Ibáñez L, Potau N, Marcos M V, De Zegher F
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Spain.
Clin Endocrinol (Oxf). 2000 Oct;53(4):523-7. doi: 10.1046/j.1365-2265.2000.01133.x.
Girls with precocious pubarche (PP) are at increased risk for ovarian dysfunction, hyperinsulinism and dyslipidaemia in adolescence, in particular when PP is preceded by reduced fetal growth. However, it is not known whether PP girls still have adrenal hyperandrogenism after puberty and if so, which fraction of PP girls develops so-called functional adrenal hyperandrogenism (FAH), an entity characterized by ACTH-dependent 17-ketosteroid excess.
Data were longitudinally collected from 47 girls with PP: at birth (weight for gestational age), at diagnosis of PP (age 6.7+/- 1.1 years) and in adolescence (age 15.0+/-1.9 years).
Serum dehydroepiandrosterone sulphate (DHEAS) and androstenedione were measured at PP diagnosis, as well as the 17-hydroxyprogesterone (17-OHP) response to ACTH; postpubertal evaluation included assessment of adrenal and ovarian function, and of insulin responses to a glucose load. PP girls were considered to have FAH in adolescence if both DHEA and androstenedione responses to ACTH were excessive (> 1500 ng/dl and > 350 ng/dl, respectively).
At diagnosis of PP, girls had high DHEAS and androstenedione levels, as well as high 17-OHP responses to ACTH. In adolescence, PP girls had a normal BMI, presented with mild hirsutism and had high baseline and post-ACTH concentrations of most adrenal androgens, low SHBG levels and tended to have hyperinsulinemia and to present biological signs of ovarian hyperandrogenism. More than a third of the PP cohort developed FAH in adolescence. Neither baseline DHEAS, androstenedione, nor post-ACTH 17-OHP values at diagnosis of PP predicted the development of FAH in adolescence. In PP girls, only a low weight at birth was found to be significantly associated with subsequent FAH.
These longitudinal findings in girls with PP point to the possibility of an endocrine sequence of prenatal onset: low weight at birth, PP in childhood and adrenal hyperandrogenism in adolescence. The pathophysiological mechanisms underpinning this newly recognized sequence remain to be identified.
阴毛早现（PP）女童在青春期出现卵巢功能障碍、高胰岛素血症和血脂异常的风险增加，尤其是在PP之前存在胎儿生长受限的情况下。然而，尚不清楚PP女童在青春期后是否仍存在肾上腺雄激素过多症，如果存在，有多少PP女童会发展为所谓的功能性肾上腺雄激素过多症（FAH），这是一种以促肾上腺皮质激素（ACTH）依赖性17-酮类固醇过量为特征的病症。
对47例PP女童进行纵向数据收集：出生时（出生体重与孕周关系）、PP诊断时（年龄6.7±1.1岁）和青春期（年龄15.0±1.9岁）。
在PP诊断时测量血清硫酸脱氢表雄酮（DHEAS）和雄烯二酮，以及17-羟孕酮（17-OHP）对ACTH的反应；青春期后的评估包括肾上腺和卵巢功能评估，以及胰岛素对葡萄糖负荷的反应。如果DHEA和雄烯二酮对ACTH的反应均过度（分别>1500 ng/dl和>350 ng/dl），则认为PP女童在青春期患有FAH。
在PP诊断时，女童的DHEAS和雄烯二酮水平较高，17-OHP对ACTH的反应也较高。在青春期，PP女童体重指数正常，有轻度多毛症，大多数肾上腺雄激素的基线和ACTH刺激后浓度较高，性激素结合球蛋白（SHBG）水平较低，且往往有高胰岛素血症和卵巢雄激素过多的生物学体征。超过三分之一的PP队列女童在青春期发展为FAH。PP诊断时的基线DHEAS、雄烯二酮以及ACTH刺激后的17-OHP值均不能预测青春期FAH的发生。在PP女童中，仅发现出生时体重低与随后的FAH显著相关。
这些对PP女童的纵向研究结果表明，可能存在一种产前开始的内分泌序列：出生体重低、儿童期PP和青春期肾上腺雄激素过多症。这种新认识的序列背后的病理生理机制仍有待确定。
